WO2014012871A1 - Oleacein for treating or preventing diseases resulting from atherosclerotic plaques - Google Patents
Oleacein for treating or preventing diseases resulting from atherosclerotic plaques Download PDFInfo
- Publication number
- WO2014012871A1 WO2014012871A1 PCT/EP2013/064869 EP2013064869W WO2014012871A1 WO 2014012871 A1 WO2014012871 A1 WO 2014012871A1 EP 2013064869 W EP2013064869 W EP 2013064869W WO 2014012871 A1 WO2014012871 A1 WO 2014012871A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- atherosclerotic plaque
- oleacein
- olacein
- diseases resulting
- atherosclerotic
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
- A61K36/638—Ligustrum, e.g. Chinese privet
Definitions
- the subject of this invention is a novel use of oleacein in the manufacturing of a preparation stabilizing atherosclerotic plaque.
- a preparation may be used in particular in the prevention and treatment of diseases caused by the degradation of atherosclerotic plaque, most specifically cerebral ischemic stroke and cardiac arrest.
- Oleacein is a compound defined by formula 1, also described in literature as 3,4-DHPEA- EDA. It constitutes a 3,4-dihydroksyfenyloetanol (hydroxytyrosol) esterified with a dialdehyde derivative of enolic acid.
- Atherosclerotic plaque is the name attributed to changes occurring in arterial walls (interior epithelium), which form in atherosclerosis.
- the plaque is composed of lipid mass (mainly LDL), cells and fibrin. It is convexed into the blood vessel lumen, decreasing its diameter. This, in turn, may lead to the ischemia of tissues supplied by the said artery.
- Atherosclerotic plaque may crack, activating serum thrombotic factors, which leads to clot formation. This may decrease vessel capacity, and in extreme cases completely occlude the vessel lumen. This is the most common manner in which the coronary artery is closed off, and in consequence heart attacks occur. In a similar fashion, the occlusion of a cerebral artery, as a result of the degradation of atherosclerotic plaque, leads to cerebral ischemic strokes. Limb ischemia may occur via a similar path.
- Atherosclerotic plaque also damages deeper layers of artery walls, contributing to the formation of aneurysms.
- Atherosclerosis it is desirable, in patients suffering from atherosclerosis, to stabilize atherosclerotic plaque. It is also desirable to stabilize damaged atherosclerotic plaque in order to decrease its rate of degradation, and thus to lessen the course of a heart attack or brain stroke.
- MMP 9 metalloproteinase-9
- type IV and V collagen metalloproteinase-9
- the goal of this invention is to deliver a preparation which could be used to stabilize atherosclerotic plaque through the successful inhibition of its degradation in the presence of metalloproteinase-9.
- a preparation could be used in the treatment and prevention of diseases arising from the degradation of atherosclerotic plaque, in particular heart attacks, coronary ischemic disease, ischemic brain stroke and limb ischemia.
- the subject of this invention concerns the use of oleacein in the manufacturing of a preparation for the treatment and prevention of diseases that are consequences of the degradation of atherosclerotic plaque, in particular those selected from a group encompassing ischemic brain stroke, heart attack as well as ischemic heart disease.
- the subject of this invention concerns also the use of oleacein in the inhibition of production of MMP-9 by the cells contained in atherosclerotic plaque.
- Next subject of this invention concerns use of olacein for reduction of atherosclerotic plaque inflammation through a change in the phenotype of existing macrophages from pro-inflammatory Ml to anti-inflammatory M2, which is important for plaque stabilisation.
- the preparation produced is used for stabilizing atherosclerotic plaque.
- the oleacein is obtained from Ligustrum vulgar e L.
- the subject of the present invention concerns also the use of Ligustrum vulgar e L. in the manufacturing of a preparation containing oleacein for stabilizing atherosclerotic plaque or for reduction of atherosclerotic plaque inflammation, particularly for the treatment and prevention of diseases that are consequences of the degradation of atherosclerotic plaque, in particular those selected from a group encompassing ischemic brain stroke, heart attack as well as ischemic heart disease.
- the present invention encompasses oleacein for any use selected of above- mentioned medical uses, any product for such use comprising oleacein, and any method, especially method for treatment human subject, comprising such use.
- Example. 1 Obtaining oleacein from the leaves of wild privet ⁇ Ligustrum vulgare L.) Wild privet (Ligustrum vulgare L.) is a decorative plant growing in Europe, often used for hedgerows. The isolation of oleacein contained in the leaves of wild privet was performed using a modification of the method by Kiss et al. (Journal of Ethnopharmacology 120 (2008) 220-225) in the Faculty of Pharmacognosis and Molecular Foundations of Phytotherapy of the Warsaw Medical Academy).
- Example 2 Stabilization of atherosclerotic plaque isolated from carotid artery.
- the unstimulated control consisted of physiological saline, in which the plaque was incubated for 2 hours.
- MMP-9 metalloproteinase-9
- the graph included in Fig. 1 shows the dependence of MMP-9 production [%] on respective oleacein concentrations (5, 10, 20 ⁇ ).
- oleacein may be used in the treatment and prophylaxis of diseases that are consequences of the degradation of atherosclerotic plaque, in particular ischemic brain stroke, heart attack as well as ischemic heart disease.
- IL-10 interleukin 10
- Oleacein-haemoglobin (OC+Hb) complexes induce the expression of the macrophage scavenger receptor CD 163, which leads to a change in the macrophage phenotypes from the pro-inflammatory Ml form to the anti-inflammatory M2 type. This process significantly affects the atherosclerotic plaque stabilisation in human arteries.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14/356,172 US9682056B2 (en) | 2012-07-14 | 2013-07-13 | Oleacein for treating or preventing diseases resulting from atherosclerotic plaques |
ES13742600T ES2711560T3 (es) | 2012-07-14 | 2013-07-13 | Oleaceína para tratar o prevenir enfermedades resultantes de placas ateroescleróticas |
EP13742600.3A EP2872131B1 (en) | 2012-07-14 | 2013-07-13 | Oleacein for treating or preventing diseases resulting from atherosclerotic plaques |
PL13742600T PL2872131T3 (pl) | 2012-07-14 | 2013-07-13 | Oleaceina do leczenia lub zapobiegania chorobom będących następstwem blaszki miażdżycowej |
DK13742600.3T DK2872131T3 (en) | 2012-07-14 | 2013-07-13 | Oleacein for the treatment or prevention of diseases due to atherosclerotic plaque |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL399962A PL227843B1 (pl) | 2012-07-14 | 2012-07-14 | Zastosowanie Ligustrum vulgare L. do wytwarzania preparatu zawierającego oleaceinę |
PLPL399962 | 2012-07-14 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2014012871A1 true WO2014012871A1 (en) | 2014-01-23 |
Family
ID=48906224
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2013/064869 WO2014012871A1 (en) | 2012-07-14 | 2013-07-13 | Oleacein for treating or preventing diseases resulting from atherosclerotic plaques |
Country Status (7)
Country | Link |
---|---|
US (1) | US9682056B2 (pl) |
EP (1) | EP2872131B1 (pl) |
DK (1) | DK2872131T3 (pl) |
ES (1) | ES2711560T3 (pl) |
PL (2) | PL227843B1 (pl) |
PT (1) | PT2872131T (pl) |
WO (1) | WO2014012871A1 (pl) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3470069A1 (en) * | 2017-10-12 | 2019-04-17 | Warszawski Uniwersytet Medyczny | Oleacein for use in atherosclerosis prevention |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2690412B1 (es) | 2017-03-10 | 2019-11-13 | Univ Sevilla | Procedimiento para la obtención de secoiridoides dialdehídicos |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009013596A2 (en) * | 2007-07-23 | 2009-01-29 | Probelte Pharma, S.A. | Fortification of nutritional products with olive extracts containing hydroxytyrosol and hydroxytyrosol fortified nutritional products |
-
2012
- 2012-07-14 PL PL399962A patent/PL227843B1/pl unknown
-
2013
- 2013-07-13 US US14/356,172 patent/US9682056B2/en active Active
- 2013-07-13 DK DK13742600.3T patent/DK2872131T3/en active
- 2013-07-13 WO PCT/EP2013/064869 patent/WO2014012871A1/en active Application Filing
- 2013-07-13 ES ES13742600T patent/ES2711560T3/es active Active
- 2013-07-13 EP EP13742600.3A patent/EP2872131B1/en not_active Not-in-force
- 2013-07-13 PT PT13742600T patent/PT2872131T/pt unknown
- 2013-07-13 PL PL13742600T patent/PL2872131T3/pl unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009013596A2 (en) * | 2007-07-23 | 2009-01-29 | Probelte Pharma, S.A. | Fortification of nutritional products with olive extracts containing hydroxytyrosol and hydroxytyrosol fortified nutritional products |
Non-Patent Citations (5)
Title |
---|
FATAR M; STROICK M; GRIEBE M; HENNERICI M: "Matrix metalloproteinases in cerebrovascular diseases", CEREBROVASC DIS, vol. 20, 2005, pages 141 - 51 |
KISS ET AL., JOURNAL OF ETHNOPHARMACOLOGY, vol. 120, 2008, pages 220 - 225 |
KISS ET AL., JOURNAL OF ETHNOPHARMACOLOGY, vol. 120, 2008, pages 220 - 225, XP025669784 * |
M. CZERWINSKA ET AL: "OLEACEIN FROM VIRGIN OLIVE OIL MAY CONTRIBUTES TO STABILIZATION OF ATHEROSCLEROTIC PLAQUES BY DECREASE MYELOPEROXIDASE RELEASE FROM NEUTROPHILS", EAS2012 ABSTRACT BOOK, 29 May 2012 (2012-05-29), pages 1108, XP055076427, Retrieved from the Internet <URL:http://www.kenes.com/eas2012/abstracts/pdf/1108.pdf> [retrieved on 20130826] * |
MONIKA CZERWISKA ET AL: "A comparison of antioxidant activities of oleuropein and its dialdehydic derivative from olive oil, oleacein", FOOD CHEMISTRY, ELSEVIER LTD, NL, vol. 131, no. 3, 20 September 2011 (2011-09-20), pages 940 - 947, XP028104623, ISSN: 0308-8146, [retrieved on 20110928], DOI: 10.1016/J.FOODCHEM.2011.09.082 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3470069A1 (en) * | 2017-10-12 | 2019-04-17 | Warszawski Uniwersytet Medyczny | Oleacein for use in atherosclerosis prevention |
CN111212636A (zh) * | 2017-10-12 | 2020-05-29 | 华沙医科大学 | 橄榄裂环烯醚萜用于动脉粥样硬化预防 |
Also Published As
Publication number | Publication date |
---|---|
US9682056B2 (en) | 2017-06-20 |
DK2872131T3 (en) | 2019-03-11 |
PL399962A1 (pl) | 2014-01-20 |
ES2711560T3 (es) | 2019-05-06 |
US20160008311A1 (en) | 2016-01-14 |
PL2872131T3 (pl) | 2019-05-31 |
PT2872131T (pt) | 2019-02-26 |
EP2872131A1 (en) | 2015-05-20 |
PL227843B1 (pl) | 2018-01-31 |
EP2872131B1 (en) | 2018-11-21 |
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